We have initiated a research focus on patients with incomplete lupus syndromes, or ILE,to develop insights into early stages of SLE (1). The ILE subset is relatively understudied and the likely outcomes are not known. Published studies are small and conflicting in terms of whether this is a stable, relatively benign phenotype or whether a progressive course is likely. The available data suggest that the ILE subset is heterogeneous, and that a subset of these individuals will progress to SLE. We hypothesize that such patients include a subset who are in the early stages of a progressive illness that culminates in SLE. We propose to determine the clinical and immunologic stability (or instability) of the ILE population and to identify biomarkers that are predictive of a progressive disease course. We believe that identification of markers of disease progression in ILE will lead to approaches to reliable, early diagnosis of SLE. Our long term goal is the development of strategies for early and reliable identification of individuals who would benefit from therapeutic interventions to prevent organ damage. We propose three aims: Aim 1: To determine the cellular changes and autoantibody profiles that are best associated with phenotypic progression in incomplete lupus (ILE)patients. Aim 2: To explore the potential of peptoid arrays to identify ILE progressors. The newly available peptoid array technology will be applied to detect shifts in the antibody repertoire on a scale that is larger than the protein array and which is not biased for known antigens. Aim 3: To determine the SLAM haplotypes and transcriptomic changes that best predict phenotypic progression in incomplete lupus patients. The long term goals of this project are to develop approaches to the identification of individuals with pre- clinical SLE. This would make feasible the design of studies to test therapeutic approaches with potential for prevention and cure.